G-protein-coupled heteromers: regulation in disease.

Over the past decade, an increasing number of studies have shown that G-protein-coupled receptors including opioid and cannabinoid receptors associate to form heteromers. Moreover, G-protein-coupled receptor heteromerization leads to the modulation of the binding, signaling, and trafficking properties of individual receptors. Although very little information is available about the physiological role of receptor heteromers, some studies have shown that the levels of some heteromers are upregulated in disease states such as preeclamptic pregnancy, schizophrenia, Parkinson's, ethanol-induced liver fibrosis, and development of tolerance to morphine. The recent generation of antibodies that selectively recognize distinct heteromers and, of peptides that selectively disrupt them, have started to elucidate the contribution of heteromers to the disease state. Here, we describe the methods for the generation of heteromer-selective antibodies and elucidation of their levels and localization under normal and pathological conditions.